The mode of action of non-specific drugs, which produce their action by concentrating in the hydrophobic regions of membranes, is poorly understood. In vivo evidence suggests that general anesthetics act by expanding some such hydrophobic region (the critical volume hypothesis). The object of this work is to test the latter hypothesis at the membrane level and to address the question of the selectivity of action of anesthetics (why aren't all membranes anesthetized?). We will measure partition coefficients of a wide variety of structural types of anesthetic (e.g. volatile, steroid, amine, alcohols) in lipid bilayers of different composition. Then we will measure the membrane expansion caused by these anesthetics in bilayers. Knowing both the partition coefficient and the membrane expansion we can calculate the molar expansion caused by the anesthetic (i.e. its partial molar volume in the membrane). Bilayer compressibility will also be measured. These parameters will be used to test the predictions of the critical volume hypothesis. The interaction between membrane protein and lipid and its effect on anesthetic partitioning and expansion will be examined in well defined rhodopsin containing bilayers as well as in acetylcholine receptor rich membranes. We will seek, thus, to distinguish two current versions of the expanded membrane concept of anesthetic action, one based on lipid, and the other on protein, expansion.